Abstracts

Rationale- Multiple experimental seizure models increase neurogenesis in the dentate granule cell (DGC) layer. To understand further the mechanisms underlying seizure-induced neurogenesis, we are investigating potential parallels between patterns of expression of molecules seen during early DGC development versus patterns observed after SE in the adult. In this study, we focused on the bHLH family of transcription factors, which is implicated in cell fate determination and differentiation in various neural systems including the dentate gyrus. We specifically sought to determine whether the expression of bHLH mRNAs is altered in the DGC layer of the adult rat after SE. Methods- Adult rats received intraperitoneal pilocarpine to induce SE using a standard protocol, and were killed 3, 7, 14, or 35d later. Brains were processed for insitu hybridization with digoxigenin-labeled probes. Results- Id-2 mRNA expression was increased in cells resembling interneurons in multiple brain regions at 3d post-SE, including the neocortex and hippocampus, as well as throughout the DGC layer. At 7d post-SE, however, Id-2 mRNA continued to increase in the DGC layer, while decreasing elsewhere. At later time points, Id-2 mRNA expression in all regions decreased to control levels. In contrast, Prox-1 mRNA expression in the dentate was reduced in 3d post-SE animals compared to controls, and slowly increased to control levels by 35d post-SE. No obvious changes in expression were seen with rat Neuro-D, Neuro D-2, and Math-2 probes. Discussion- These findings show that prolonged seizures in the adult rat alter the expression of proteins that are normally expressed during early dentate gyrus development. It remains to be determined whether the inverse relationship between the post-SE pattern of expression of Id-2 (a bHLH protein with anti-neurogenic activity) and Prox-1 (a marker of mature DGCs) is functionally significant. However, these findings support the idea that molecules controlling cell fate decisions in the developing dentate gyrus are also operative during seizure-induced neurogenesis in the adult.Supported by NIH N535628, AES, and EFA.